Vascularization of many solid tumors occurs in vivo as a consequence of the vectorial growth of host capillary endothelial cells along a concentration gradient of a tumor-produced, diffusible angiogenesis factor (AF). Our studies of this process primarily employ an angiogenesis assay on the chicken chorioallantoic membrane and two in vitro assays that examine effects of tumor-derived agents on the growth and migration properties of cultured endothelial cells from fetal bovine aorta. Several components of the ethanol extracts from lyophilized cell homogenates of the Walker 256 rat tumor, which display any or all of these activities, have been tentatively identified using primarily chromatographic and spectroscopic techniques. These substances, products from ischemic tissue metabolism-adenosine, inosine and hypoxanthine (from ATP degradation) as well as nicotinamide (from NAD), appear to be angiogenic and chemotactic for EC, but not mitogenic for EC. Future studies will seek (1)\to confirm these early findings by additionally using the corneal micropocket angiogenesis assay; (2)\to determine for these agents their mechanism of action by conventional methods, e.g., by using analogs, radiolabeled materials, etc.; (3)\to identify EC mitogenic material also present in the extracts from the Walker tumor; (4)\to conduct, using techniques developed from these rat tumor studies, a comparative survey on the angiogenic activity and AF molecules present in a variety of tumors that, in situ, differ in vascularization; and (5)\to perform a similar survey on the angiogenic properties of homogenates from normal tissues and of ultrafiltrates from animal sera, including sera from tumor-bearing animals. Through our efforts to better understand tumor vascularization in terms of specific factors which affect specific cell functions, we hope to provide improved means for controlling tumor growth and spread and for detecting solid tumors.